The eye, which is responsible for vision, is probably the most remarkable organ in animals. It is comprised of many complex components, for example, cornea, aqueous humor, lens, vitreous and retina, with each having its own highly specialized function contributing significantly to the overall visual experience. Unfortunately, each section of the eye is susceptible to well-known pathological disorders which can reduce the quality of vision and/or resulting in partial or total blindness. Such pathological processes comprise vitreous liquefaction and opacification, retinal detachment, glaucoma, and opacification of the lens and cornea.
The vitreous is a remotely oxygenated transparent mass that in most animals is physically a gel-like substance. It consists predominantly of water and fills the posterior chamber of the eye. The vitreous functions to give shape to the eye, transmit light, and form a semi-solid support for the retina against the choroid. When the vitreous is physically altered or becomes opaque, permanent blindness can develop. For example, should the vitreous partially liquify, as it often does with age, its supporting capability is diminished and retinal detachment may result. It is well appreciated that retinal detachment is the leading cause of blindness in the United States.
Furthermore, the vitreous may become opaque as a direct consequence of cellular infiltration or hemorrhage. Cellular infiltrations are common in a number of inflammatory processes of tissue surrounding the vitreous. As a result of inflammation, opacification degeneration of the vitreous may be seen. Vitreous hemorrhage is also very common, particularly in diabetics, and occurs when the retina ciliary body ruptures and hemorrhages into the vitreous developing large opaque areas. Unlike most other tissue, however, the vitreous is avascular and does not contain significant macrophages. Therefore, if foreign agents or blood penetrate into the vitreous, they may permanently remain in the vitreous thereby leading to partial or total vision impairment. In either disease process, liquefaction or opacification of the gel-like substance, vitreous replacement with a suitable substitute is required.
For several years, surgical removal and replacement of the vitreous with a less than optimal substitute has been known. Vitreous replacement has been accomplished by a variety of liquids including salt solutions, vitreous humor from animals, spinal fluids and other substances thought to have desirable properties. Survey of Ophthalmology: "A Review Of Substances And Techniques Of Vitreous Replacement" by G. H. Peyman, E. S. Ericson and D. R. 17:41-51, May, 1972. Silicone oils (dimethylsiloxanes of various viscosities) have been used for partial replacement of vitreous humor with success but have doubtful application because of pathological changes after long term replacement. New England Journal of Medicine: "Alloplasty In Surgery Of The Eye" by W. Stone, Jr., 258:486-490, 1958. There also have been reported results from the use of lyophilized vitreous, pure hyaluronic acid, or polygeline and the use of collagen is still in its experimental stage. Gloor, B.P.M.P.IN: Moses R. A. (Pd.) alters physiology of the eye. Clinical application. 7th Ed. St. Louis: C. V. Mosby Company, p. 270 (1971). Biochimica et Biophysica Acta: "Studies On Hyaluronic Acid". The Preparation And Properties Of Rooster Comb Hyaluronic Acid" by D. A. Swann, 156: 17-30 (1968) and U.S. Pat. No. 4,141,973, issued Feb. 27, 1979 to Balazs.
Out of the presently available vitreous replacements, salt solutions, silicone oils and hyaluronic acids are predominantly used even though they are less than optimal substitutes with each having its own major disadvantages. Salt solutions are not readily compatible with the retina or the optic nerve, yielding some disintegration of vision, changes at the end of the optic nerve and retinal unhealthiness. Silicone oils, in addition to their toxicities, also tend to emulsify and break-off into droplets, a process often called "fish-egging", thereby enhancing their turbidity. Finally, hyaluronic acid is very expensive, difficult to produce and has a fixed viscosity. Since hyaluronic acid is derived from rooster combs, its supply is limited.
Most knowledge of present vitreous replacement concerns the uses of gases such as air, nitrogen, and sulfurhexafluoride. The first fluorocarbon to be used as a gas in the vitreous was octafluorocyclobutane or perfluorocyclobutane. Archives of Ophthamology: "Octafluorocyclobutane And Other Gases For Vitreous Replacement" by C. M. Vygantas, G. A. Peyman, M. J. Daily and E. S. Ericson 90:235-236, 1973. Other perfluorocarbon gases more recently tested are perfluoromethane, perfluoroethane and perfluoropropane. Archives of Ophthamology: "Intravitreal Longevity Of Three Perfluorocarbon Gases" by H. Lincoff, J. Mardirossian, A. Lincoff, P. Ligett, T. Iwamoto and F. Jakobjec, p. 1610, 1980. Perfluoro-n-butane and perfluoroisobutane have also been studied. Vitreous Surgery And Advances In Fundus Diagnosis And Treatment, "Octafluorocyclobutane (C.sub.4 F.sub.8) Gas As Vitreous Replacement" by C. M. Vygantas pp. 423-425, 1975. These gases are being used because they are biologically inert, insoluble in water and pass through membranes very slowly. They, therefore, equilibrate with blood gases (O.sub.2, CO.sub.2, N.sub.2) in the vitreous and reach an equilibrium condition after hours or days. The equilibrium finally reached is a function of the partial pressure of the particular gas as well as the blood gases. However, since perfluorocarbon gases are compressible, they will remain in an equilibrium state only as long as the gas pressure is essentially unchanged. For example, the gases would increase in volume during an airplane flight while their volume would probably also change during anesthesia because most anesthetic gases rapidly diffuse through body tissues. Fluorinated anesthetics might represent particularly complicated gas-vapor level equilibrium. Because of these undesired properties, among others, perfluorocarbon gases are less than optimal as vitreous replacements. However, in spite of considerable work reported in connection with vitreous replacement, as set forth herein above, there is no ideal gelatinous substitute for the complex glycoprotein structure of the vitreous body. Known vitreous replacements are not completely satisfactory because they may cause post-operative complications resulting in total blindness. Vitreous substitutes, thus, have somewhat fallen into disrepute because basic researchers have had difficulty introducing a substitute that is clear, inert, well tolerated, and remains viscous long enough.
The retina comprises the innermost tunic of the eyeball containing the nervous elements for reception of visual stimulae. The phenomenon of detachment of the retina consists of physical separation of the retina from its juxtaposition to the choroid. The most important factor contributing to retinal detachment is liquefaction and shrinkage of the vitreous, commonly known as vitreous retraction. In addition, vitreous retraction generated by vitreous shrinkage may produce retinal tear with or without retinal detachment. There are presently three methods of treatment for retinal tear with or without retinal detachment. The first consists of scleral buckling (forcing the anterior wall of the choroid against the posterior side of the retina) which utilizes an external encircling band in retinal tears and detachments. Also, removal of the entire vitreous gel from the vitreous cavity may be utilized in retinal detachment. However, this procedure is utilized only in extreme cases. The third method requires the patient to lie on his ventral surface while the physician introduces into the posterior chamber an air bubble (having a specific gravity less than vitreous fluid) in order to force the detached retina back against the choroid. Moreover, the patient must remain on his ventral surface during the early recovery stage, perhaps for many days. All three forms of treatment appear to be quite inconvenient to the patient as well as to the physician, and constitute somewhat extreme methods of treatment.
The aqueous humor is the fluid produced in the eye which fills the anterior chamber, located between the cornea and the lens. Because aqueous humor is being produced constantly, its rate of formation and exit from the eye is directly related to the steady straight level of intraocular pressure. In "glaucoma", elevated intraocular pressure is related to the eye's reduced capability to facilitate outflow of aqueous humor. Thus, the abnormally high pressure squeezes against the retina, occluding circulation in the choroid and retina, the optic disk becomes distorted and concave, and blindness results. The primary treatment for glaucoma presently is to medicate the eye with a drug that decreases the rate of aqueous humor formation. The present course of therapy is to suppress the rate at which aqueous humor is formed. But it appears possible to totally replace the aqueous humor in glaucoma. The problem with replacing aqueous humor, however, is to find a suitable substance. Heretofore, there have been no attempts to replace the aqueous humor with substitutes.
The cornea and lens are normally transparent to provide refracting surfaces for the optical system of the eye. Any change in the transparency of the cornea or the lens will seriously interfere with the clarity of the retinal image. Nevertheless, the cornea and lens are subject to loss of transparency and will develop opacity depending upon the disease process as to which each may be affected. Presently, the opaque areas in the cornea and lens are surgically removed. In addition, the lens is often totally removed, for example in cataract surgery. The undesirable complications that can develop from surgical treatment of opaque areas within the cornea and lens are well known. Moreover, if surgical removal of the opaque areas is successful, vision will probably remain impaired and even possibly incorrectable.
It is apparent from the above brief overview of various disorders of the eye and the current state of knowledge that there are critical needs which must be met, and problems to be solved, so that the precious phenomenon of eyesight may be either restored or preserved.